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Glutathione in fish : transport, influence of temperature and growth rate, and interaction with the stress response Leggatt, Rosalind Alexandra


Glutathione (GSH) is a ubiquitous antioxidant involved in many cellular processes in mammals. In contrast, fish have relatively low GSH levels, as well as low turnover and activity of associated enzymes. As the metabolism and function of GSH have been poorly studied in fish, I examined the mechanisms by which fish tissues transport GSH, the influence acclimation temperature and growth rate have on GSH dynamics, and the importance of GSH during heat stress in fish to elucidate the differing roles of GSH in fish and mammals. In Chapter 2 I demonstrated that posterior kidney, and to a lesser extent liver and gill, of rainbow trout took up GSH by extracellular breakdown and intracellular synthesis. Direct uptake of exogenous GSH was observed in the liver as apparent gradient-dependent transport. In Chapter 3 I demonstrated that GSH turnover was proportional to incubation temperature in a rainbow trout hepatoma cell line in vitro. In killifish in vivo, tissue GSH levels and activity of GSH-associated enzymes were proportional to acclimation temperature. Although these experiments showed that temperature influences GSH dynamics in fish, the effects of temperature could only partially explain the low GSH levels in fish compared with mammals. In Chapter 4 I showed that high GSH levels and activity of associated enzymes in growth hormone transgenic coho salmon with high metabolic rates were due to increased feeding and growth rather than to direct effects of the transgene. Oxygen consumption corresponded to liver GSH levels in control and transgenic fish, but not to other components of the GSH system. Although long-term changes in temperature influenced GSH dynamics in killifish, in Chapter 5 I demonstrated that acute temperature changes had little effect on GSH dynamics in rainbow trout in vivo or in vitro. However, altered GSH levels inconsistently altered the cellular response to acute heat stress in rainbow trout in vitro, and influenced the generalized and cellular responses to acute heat stress in vivo. Taken together, these studies demonstrate that fish can substantially modulate GSH levels in response to demand, and that altered GSH levels influence other physiological systems.

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